| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| Targets |
Itanapraced targets gamma-secretase, an enzyme complex involved in the cleavage of the amyloid precursor protein (APP). As a modulator, it alters the enzyme's activity to reduce the production of the more toxic Aβ42 peptide, while sparing other cleavage products.
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| ln Vitro |
The suspension of APPswe in human neuroastroma cells (H4swe) is inhibited by itanapraced (0.03-100 μM), with IC50 values of 3.6 and 18.4 μM for Aβ42 and Aβ40, respectively [1]. At doses up to 15, itanapraced (5-200 μM) quantitatively controls action potential. The IC50 value of itanapraced (0-1000 μM; 30 min) is 106 μM [2]. In HEK293swe cells, itanapraced (30-100 μM) suppresses Notch processing at quantitatively adjusted μM [1]. The fluorescence of hippocampal neuron cells caused by hypoxia switch (OGD) can be greatly reduced by itanapraced (1-10 μM) [2].
In human neuroglioma cells expressing the Swedish mutant form of APP (H4swe), Itanapraced reduces Aβ42 and Aβ40 secretion with IC50 values of 3.6 and 18.4 μM, respectively. This demonstrates its potent modulatory activity on gamma-secretase in a cellular model of amyloid production. |
| ln Vivo |
Itanapraced (face; 375 ppm given to diet, 17 weeks) lowers Aβ42 and Aβ40 levels and brain plaque load in Tg2576 button mice [1].
In vivo, Itanapraced attenuates brain beta-amyloid pathology and learning deficits in a mouse model of Alzheimer's disease. It inhibits oxygen glucose deprivation (OGD)-induced apoptosis in hippocampal neurons, suggesting a neuroprotective effect. |
| Enzyme Assay |
The activity of Itanapraced as a gamma-secretase modulator is assessed in cell-free assays using purified gamma-secretase or membrane preparations. The compound's effect on the production of Aβ peptides (Aβ40 and Aβ42) is measured by ELISA or mass spectrometry. Its IC50 is determined in these assays.
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| Cell Assay |
In vitro cellular assays are performed using cell lines that overexpress APP, such as the H4swe neuroglioma cell line. Cells are treated with Itanapraced, and the levels of Aβ40 and Aβ42 in the culture medium are measured by ELISA. The compound's potency as a GSM is determined from its IC50 values.
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| Animal Protocol |
Animal/Disease Models: Male and female Tg2576 transgenic mice expressing the Swedish mutant form of human APP (APPswe) [1]
Doses: 375 ppm Route of Administration: Oral; 375 ppm in diet for 17 weeks Experimental Results: Aged Tg2576 mice Total brain Aβ42 and Aβ40 levels and brain plaque burden were diminished. It does not cause COX-mediated toxic effects in the gastrointestinal tract and does not cause Notch-mediated cell differentiation abnormalities in the ileum. In vivo efficacy is evaluated in transgenic mouse models of Alzheimer's disease that overexpress mutant human APP. Animals are treated orally with Itanapraced, and its effects on brain Aβ levels, amyloid plaque deposition, and cognitive function are assessed. |
| ADME/Pharmacokinetics |
Itanapraced is an orally active compound. Its pharmacokinetic properties have been studied in preclinical models. It can cross the blood-brain barrier to reach its target in the brain. It has a molecular weight of 285.12 g/mol and a formula of C16H11Cl2FO2.
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| Toxicity/Toxicokinetics |
Toxicological data for Itanapraced is not fully detailed in the provided sources. As a drug candidate, it would have undergone standard preclinical safety evaluations. It is structurally related to NSAIDs, suggesting a potential for gastrointestinal effects, though this may be mitigated.
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| References |
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| Additional Infomation |
Itanapraced is a gamma-secretase modulator that has been investigated as a potential disease-modifying therapy for Alzheimer's disease. Its dual mechanism, combining GSM activity with anti-inflammatory properties, is of particular interest. It represents a promising approach to reducing Aβ pathology.
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| Molecular Formula |
C16H11CL2FO2
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|---|---|
| Molecular Weight |
325.1604
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| Exact Mass |
324.012
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| Elemental Analysis |
C, 59.10; H, 3.41; Cl, 21.80; F, 5.84; O, 9.84
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| CAS # |
749269-83-8
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| PubChem CID |
9996409
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| Appearance |
White to off-white solid powder
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| LogP |
4.915
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
21
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| Complexity |
413
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC(C1(CC1)C(C=C2)=CC(F)=C2C3=CC=C(Cl)C(Cl)=C3)=O
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| InChi Key |
LIYLTQQDABRNRX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H11Cl2FO2/c17-12-4-1-9(7-13(12)18)11-3-2-10(8-14(11)19)16(5-6-16)15(20)21/h1-4,7-8H,5-6H2,(H,20,21)
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| Chemical Name |
1-[4-(3,4-dichlorophenyl)-3-fluorophenyl]cyclopropane-1-carboxylic acid
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| Synonyms |
CHF 5074; CHF-5074; CHF5074
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~307.54 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (7.69 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0754 mL | 15.3770 mL | 30.7541 mL | |
| 5 mM | 0.6151 mL | 3.0754 mL | 6.1508 mL | |
| 10 mM | 0.3075 mL | 1.5377 mL | 3.0754 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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